BALB/c myeloma protein can function as tumor-specific transplantation antigens (Lynch, Graff, Sirisinha, Simms and Eisen, PNAS 69:1540-44, 1972). The immunity induced by myeloma proteins is directed against the idiotypic determinants of the immunoglobulin molecule which are clone-specific, and are located in or near the DNP-ligand binding sites of these proteins. We have demonstrated this with two IgA myelomas, MOPC-315 and MOPC-460, both of which are anti-DNP myelomas. This system offers the advantages of large amounts of purified, highly characterized tumor-specific transplantation antigen and host immunity directed to a site on this antigen which has been localized and which can be blocked by DNP-hapten. We propose: (1) to study the host mechanisms which operate in myeloma-immunized mice to render them resistant to lethal numbers of cells; (2) to study the host defense mechanisms which operate in non-immune mice innoculated with non- tumorogenic numbers of myeloma cells; and (3) to determine if mice bearing advanced plasmacytomas can be rendered specifically immune to the plasmacytoma and maintained in permanent remission. Achievement of the long-term goals may have implications for human myeloma.